Premium
Apolipoprotein E and obstructive sleep apnea: evaluating whether a candidate gene explains a linkage peak
Author(s) -
Larkin Emma K.,
Patel Sanjay R.,
Redline Susan,
Mignot Emmanuel,
Elston Robert C.,
Hallmayer Joachim
Publication year - 2006
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20127
Subject(s) - apolipoprotein e , locus (genetics) , genetics , genotype , allele , genotyping , genetic linkage , biology , medicine , disease , gene
Evidence from both linkage analyses and association‐based analyses has implicated Apoliprotein E ( ApoE ) as a disease susceptibility locus for obstructive sleep apnea. To further assess the putative role of ApoE in sleep apnea, we performed genotyping, association, and linkage analyses in a cohort assembled to investigate the genetic epidemiology of sleep apnea. Among a subset of the Caucasian families, ten microsatellites, spanning 20 cM, were genotyped in a region near ApoE on chromosome 19 where previous suggestive linkage had been demonstrated using a 9.1‐cM genome‐wide scan. Haseman‐Elston regression analysis, conducted with these fine mapping markers (n=196 sibling pairs, 56 families), showed evidence for linkage to marker AFM210yg9 ( p =0.00034), which was increased over that observed with the original scan. ApoE genotyping also was performed on a larger set of data (n=1,211 from 271 families, ages 3–85 years) from the cohort with available DNA. To determine whether the ApoE genotype explains the linkage peak, we included the ApoE genotype as a covariate in regression models. Inclusion of ApoE E2 allele as a covariate reduced the regression coefficient by 18%, suggesting that ApoE does not substantively explain the linkage signal. Finally, we repeated an association‐based analysis in the larger sample of 1,211 individuals, and observed a higher prevalence of sleep apnea among individuals with the ApoE E2 allele. Overall, the evidence suggests that there is a disease susceptibility locus for obstructive sleep apnea in the region of ApoE , but ApoE itself is unlikely to be the causative locus. Genet. Epidemiol. 2006. © 2005 Wiley‐Liss, Inc.